Congenital And Cystic Renal Disease

Question 1

Gross Anatomy of the Kidney:

1. Cortex
2. Medulla

Answer 1

1. Cortex
   
   • usually ~ 1 cm thick, contains glomeruli, proximal tubules and distal tubules
2. Medulla
   
   • divided into 8-18 medullary pyramids and contains loops of Henle and collecting ducts

Question 2

1-1.5 million nephrons composed of:

Answer 2

1. Glomerulus –
   
   • supplied by afferent arteriole ⇒ glomerular capillaries ⇒ efferent arteriole
2. Proximal tubule –
   
   • first segment of nephron after Bowman’s capsule
   • epithelium with brush border
3. Loop of Henle –
   
   • begins at transition from thick-walled to thin-walled tubule
4. Distal tubule –
   
   • thick ascending limb merges with distal tubule
5. Collecting duct –
   
   • receives ~6 distal tubules and enters medulla
   • join each other to form ducts of Bellini which drain into calyx

Question 3

Describe the Glomerular Endothelial Cells:

Answer 3

• Fenestrated (70-100 nm)
• Negatively charged surface
• Form initial filtration barrier
• Synthesize and maintain GBM

Question 4

What is the Glomerular Basement Membrane (GBM)?

Answer 4

• Composed Type IV collagen
• Size and charge are main determinants of filtration:
  
  • Heparan sulfate provides negative charge
  • Water and cationic proteins of LMW (are permeable
  • Albumin permeability is limited by its negative charge

Question 5

What is the role of the Visceral Epithelial Cells (Podocytes)?

Answer 5

• Also synthesize and maintain GBM
• Cytoplasmic foot processes form filtration slit (slit pore)
• Podocytes are negatively charged

Question 6

What is the role of the Mesangial Cells?

Answer 6

• Cell cytoplasm contains myosin filaments
• Cells are surrounded by GBM like matrix
• Provides structural support
• Modulate glomerular filtration

Question 7

What are the different types of congenital renal abnormalities?

Answer 7

1. Aplasia, Hypoplasia, dysplasia
2. Ectopic kidneys
3. Fusion abnormalities
4. Duplication of ureters

Question 8

• What is the most common congenital kidney disorder?
• What are characteristics of this disorder?

Answer 8

Horseshoe Kidney

• 90% are fused at the lower pole
• Increased incidence with Turner’s syndrome
• Increased risk of infection and kidney stones

Question 9

Renal Dysplasia:

• **Incidence: **
• Detection:

Answer 9

• Incidence:
  
  • Unilateral – 1 in 4,300 live births
  • Combined incidence – 1 in 3,600
• Detection:
  
  • Prenatal ultrasound
  • Palpable mass
  • Asymptomatic (undetected into adulthood)

Question 10

What is the genetic defect in Autosomal Recessive PKD?

Answer 10

PKHD1 gene located on chromosome 6p21

• Can be diagnosed in utero by ultrasound:
  
  • large hyperechoic kidneys
  • oligohydramnios
  • decreased urine in fetal bladder

Question 11

How does ARPKD present?

Answer 11

• Enlarged kidneys at birth
• Serious cases incompatible with life
  
  • Perinatal mortality 30-50%
• Associated with maternal oligohydramnios
  
  • Potter’s facies
  • Pulmonary hypoplasia

Question 12

What are the main extrarenal manifestations of ARPKD?

Answer 12

1. Hepatic fibrosis
2. Cholangitis
3. Portal hypertension
   
   • esophageal varices
   • GI bleeding

Question 13

**ARPKD: **

Morphology

Answer 13

• Smooth kidney with numerous small cysts
  
  • Cortical and medullary cysts
• Cut section – cylindrical cysts extending radially through cortex
• Microscopically – cysts lined by cuboidal epithelium; may see epithelial hyperplasia
• Glomeruli normal

Question 14

• How is family hx relevant in Autosomal Dominant PKD?
• What is the genetic defect in Autosomal Dominant PKD?

Answer 14

• Affects 1:400 - 1:1000 Americans
• Family history absent in 25-40%
  
  • new mutations
  • late-onset renal failure
• 90% have mutation of PKD1 gene on chr. 16
  
  • Others have mutation of PKD2 gene on chr. 4
  • Patients with PKD2 mutations progress to renal failure at a later age than PKD1

Question 15

ADPKD

Cyst Formation

Answer 15

• Abnormal differentiation of epithelial cells
• High proliferation rate
• Secretion of fluid into cysts with loss of connection to functioning nephrons
• Abnormal extracellular matrix

Question 16

What are the renal manifestations in ADPKD?

Answer 16

• hematuria and mild proteinuria
• hypertension
• progressive renal failure
  
  • 50% reach ESRD by age 57-73
• infections
• stones
• pain

Question 17

What are the extrarenal manifestations in ADPKD?

Answer 17

• Hepatic cysts (40%)
• Intracranial aneurysms (10-30%)
• Cardiac valvular abnormalities
• Arterial aneurysms (aorta, coronaries)
• IVC thrombosis
• Inguinal & umbilical hernias
• Pancreatic cysts

Question 18

ADPKD:

Diagnosis

Answer 18

Patients present in several different ways:

• symptomatic presentation: typically flank pain & hematuria
• multiple bilateral cysts noted incidentally on imaging study
• screening due to family history with ultrasound:
  
  • Age <30: at least 2 cysts
  • Age 30-59: at least 2 cysts in each kidney
  • Age >60: at least 4 cysts bilaterally

Question 19

What are the treatment goals for ADPKD?

Answer 19

• Slow the progression to ESRD (end stage renal disease)
  
  • Control blood pressure
  • Treat infections
• Identify and manage extrarenal manifestations
• Control pain
• Dialysis/Kidney Transplant

Question 20

What is the main cause of Acquired Cystic Disease?

Answer 20

• Develop in 50% of patients on dialysis and depends on duration of dialysis
  
  • more likely with more years on dialysis
• Usually asymptomatic, but may present with bleeding or pain

Question 21

• Describe the cysts associated with Acquired Cystic Disease:
• What can Acquired Cystic Disease lead to?

Answer 21

• Clear, fluid-filled cysts
  
  • Uni- or multilocular cysts
  • Cortex (usually), may involve corticomedullary junction and medulla
• Increased incidence of papillary renal cell carcinoma

Question 22

What are the indications for renal biopsy?

Answer 22

• Persistent glomerular hematuria
• Persistent nephrotic range proteinuria
• Unexplained renal failure
• Renal transplant rejection

Question 23

What are contraindications to renal biopsy?

Answer 23

• Bleeding disorders
• Anatomic abnormalities (e.g. solitary kidney)

Question 24

What are complications that can result from a renal biopsy?

Answer 24

• Self limited gross hematuria (10%)
• Hematoma formation (80% of cases)
• Hemorrhage (1-2% of cases)
  
  • Surgery requiring (0.3% of cases)
• Death (1/8000 cases)

Question 25

What are the routine studies performed on a renal biopsy?

Answer 25

• Light microscopy:
  
  • silver, trichrome, PAS, H&E stains
• Direct immunofluorescence microscopy:
  
  • IgA, IgG, IgM, C3, C1q, albumin, fibrinogen, kappa, lambda
  • Identifies patterns of immune-complex deposition
• Electron microscopy:
  
  • submicroscopic defects and site of damage in glomerulus